Human retinal progenitor cell transplantation to preserve vision

By Lesley Wassef

The transplanted RFP-tagged p53−∕− MRPs (red) formed an epi-retinal tissue onto the retinal ganglion cell layer 3 weeks post transplantation. A subset of cells expressed retinal ganglion cell markers such as Brn3 (A and B), Islet1 (C and D, small white arrows) and Tuj1 (E and J). Incorporation of transplanted cells into the retinal ganglion cell layer was also observed (H–J). Scale bars, 25m (A and B) and 50 m (C–J). Click on the image to see a larger version of it.

Photoreceptor cells in the retina are involved in detecting light and converting it into neural signals for vision. Retinal degenerative diseases, such as age-related macular degeneration, are the leading cause of blindness in the developed world. While very few effective treatments exist to slow the progression of these diseases, a new study in The Journal of Biological Chemistry provides what the authors say is proof of concept that dying photoreceptors can be rescued by cell transplantation.

The study, led by Kang Zhang at Central South University in China and conducted with collaborators in the U.S. and Europe, set out to determine whether transplanted human retinal progenitor cells, or hRPCs, have protective or restorative effects. After all, many lives have been saved by replacing dying organs through transplantation. In addition, studies in animal models of retinal degenerative diseases have demonstrated that transplanted retinal progenitor cells can migrate into the retina and differentiate into photoreceptor cells.

So the team turned to a widely used animal model for inherited retinal degeneration: the Royal College of Surgeons, or RCS, rat. In one group, the researchers injected hRPCs (in solution) into the retina of only one eye per rat, leaving the other eye as a control. Two additional groups of rats were used as well: One group was injected with a vehicle (solution without the hRPCs), and another group was not injected at all.

The researchers report that 12 weeks after the injection, only the eyes that had been injected with hRPCs showed preservation of visual acuity (i.e., clarity), whereas deterioration was seen in eyes of RCS rats that had not been injected.

Zhang

Further testing showed that hRPCs preserved the outer nuclear layer by increasing its thickness, increasing the number of cells and increasing the spread of cells. The results, the researchers say, are believed to be a result of hRPCs rescuing the host photoreceptors through the delivery of the right ingredients (for example, neurotrophic factors) rather than cell replacement.